The immunohistochemical expression of DF3 antigen and serum concentrations of CA15-3, a breast carcinoma-associated antigen recognized by the monoclonal antibodies (MAbs) 115D8 and DF3, was investigated in breast cancer patients. The levels of serum CA15-3 in 23 primary breast cancer patients did not correlate to the percentage cytoplasmic reactivity of MAb DF3 with the carcinoma cells in tissue specimens from each respective patient. In 17 patients who subsequently developed metastatic breast cancer, however, the serum CA15-3 concentrations generally correlated well to the cytoplasmic reactivity of MAb DF3 with the carcinoma cells in specimens obtained at initial biopsy or mastectomy. Elevated levels of serum CA15-3 were seen in metastatic breast cancer patients when the carcinoma cells in their primary specimens expressed enhanced levels of cytoplasmic DF3 antigen. The results of this study suggest that the immunohistochemical demonstration of DF3 antigen in tissue specimens, together with the periodical measurement of circulating CA15-3 antigen, may be important for monitoring the clinical course of breast cancer patients.